Miguel Bronchud, Co-Founder and Director of Clinical Research at BO REAL BioTech, shared on LinkedIn:
“Unlike monocytes that are constantly renewed from bone marrow hematopoietic stem cells throughout life, resident microglia in the healthy brain persist during adulthood via constant self-renewal.
Their ontogeny, together with the absence of turnover from the periphery and the singular environment of the central nervous system, make microglia a unique cell population.
Title: Cellular and Molecular Characterization of Microglia: A Unique Immune Cell Population
Authors: Carole Sousa, Knut Biber, Alessandro Michelucci.
Read The Full Article.
A non-linear biological transition occurs around age 50, driving major changes in gene regulation, DNA methylation, chromatin access, and 3D genome architecture.
Astrocytes experience impaired ATP synthesis and a slow, steady loss via lysosomal autophagy at about 0.2% per year from age 20.
Authors from La Jolla say the key to human brain aging is ‘Microglial Replacement’?
Original resident brain microglia are progressively replaced by highly inflammatory peripheral monocytes originating from the bone marrow.
Eric Topol also makes some interesting observations and reviews on this topic.
Read further here.
This phenomenon recently described by the La Jolla team is potentially very important because (among other reasons) it can on one hand help us to explain age dependent memory loss in humans (as suggested above ); and on the other hand, any such selective cellular migration could perhaps be used to deliver locally (in a highly precise and accurate manner) any CNS active substances of potential psychiatric therapeutics relevance.
Peripheral Blood Monocytes home into specific human tissues through a multistep process often called the leukocyte adhesion cascade (LAC).
As a classic example, during skin inflammation or infection, local cells release chemical signals that guide circulating monocytes out of the blood vessels and into the injured dermal tissue.
In the injured skin tissue releases pro-inflammatory cytokines (including TNF-alpha and IL-1). Local blood vessel lining cells (endothelium) activate and display surface proteins called P-selectin and E-selectin.
Fast-flowing monocytes catch these selectins with their own surface glycoproteins, causing them to slow down and roll along the blood vessel wall.
Endothelial cells present specific chemical attractants called chemokines (such as CCL2/MCP-1) on their surface.
Monocyte chemokine receptors catch these signals, triggering “inside-out” activation of their surface integrins (like VLA-4 and LFA-1).
These activated integrins lock tightly onto endothelial counter-receptors (like ICAM-1 and VCAM-1), bringing the rolling monocyte to a complete stop.
Transmigration usually involves that a firmly attached monocyte flattens and crawls along the endothelial surface to find a cell-to-cell junction. It squeezes through the gaps between endothelial cells and breaches the basement membrane to enter the targeted skin tissue, guided by the highest concentration of the chemical attractant.
Research should now explore LAC in the brain”
You can also read: Neurological Side Effects of Cancer Immunotherapy
